Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.
Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.
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DOI：
10.1371/journal.pone.0034158
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wise MJ
中科院分区：
文献类型：
--
作者：
Anderson AM;Carter KW;Anderson D;Wise MJ
内分泌干扰物通过扰乱核受体信号系统引起不良的健康影响。据推测，这些化合物也可能扰乱表观遗传机制，从而有助于成人发病疾病的早期起源。我们假设组蛋白甲基化可能是易受干扰的表观基因组的一个组成部分。我们使用公开数据的共表达分析来研究正常睾丸中核受体和参与组蛋白甲基化的基因在面对内分泌干扰物时的组合作用。在人类、大鼠和小鼠的睾丸组织中，以及从四次大鼠毒性实验中获得的对照和暴露样本中，对一组基因的表达模式进行了分析。我们的研究结果表明，组蛋白甲基化事件是睾丸中核受体介导的转录调控的一个更普遍的组成部分。共表达模式支持涉及组蛋白甲基化修饰因子Kdm1、Prdm2和Ehmt1的看门人机制的作用，并表明该机制是与内分泌干扰相关的各种生理终点至关重要的基因转录完整性的共同决定因素。暴露于vinclozolin和邻苯二甲酸二丁酯后的共表达模式表明，特别是去甲基化酶Kdm1的协同活性值得进一步研究，以确定其与内分泌干扰物的作用方式有关。这项研究提供了一个概念的证明，即生物信息学方法可以在多个生物环境中描述与特定假设相关的基因，可以为在个体实验水平或通过传统的差异表达分析方法难以辨别的共调节活性提供强有力的见解。
Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.
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影响因子：
14.9
作者：
Kim SM;Kim JY;Choe NW;Cho IH;Kim JR;Kim DW;Seol JE;Lee SE;Kook H;Nam KI;Kook H;Bhak YY;Seo SB
通讯作者：
Seo SB
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12.3
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通讯作者：
Zhang J
影响因子：
64.5
作者：
Garcia-Bassets, Ivan;Kwon, Young-Soo;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
影响因子：
16.8
作者：
Brykczynska, Urszula;Hisano, Mizue;Peters, Antoine H. F. M.
通讯作者：
Peters, Antoine H. F. M.
影响因子：
11.2
作者：
Dreijerink, Koen M. A.;Mulder, Klaas W.;Timmers, H. Th. Marc
通讯作者：
Timmers, H. Th. Marc